Daniel A. N. Barbosa, M.D., is a Research Fellow working under the mentorship of Dr. Casey H. Halpern (Assistant Professor of Neurosurgery) and Dr. Jennifer McNab (Associate Professor of Radiology). He received his medical degree from the Federal University of the State of Rio de Janeiro in 2018. During his clinical education, Dr. Barbosa followed several renowned neurosurgeons and neurologists, and had a large experience with neurological and psychiatric patients. He developed great interest for the investigations of neurosurgical techniques to improve brain function. The invaluable experiences with these patients shaped a great interest on the investigations of neurosurgical techniques to improve brain function. His clinical and academic training together with the research experience provided him with an excellent background in multiple biological disciplines including neurosurgery, neurology, psychiatry, and neuroimaging. He also had the opportunity of joining a team of neurosurgeons and clinical scientists in the largest clinical study on deep brain stimulation for morbid obesity to date. With Drs. Ricardo de Oliveira-Souza, Alessandra Gorgulho, and Antônio De Salles (UCLA Emeritus Professor of Neurosurgery), Dr. Barbosa has led a systematic review on the topic. He also worked on the development and the publishing of this study protocol as well as that of a clinical trial of a novel neurosurgical therapy for depression. During his graduate career, these clinical investigations generated several peer-reviewed publications, book chapters, and conference presentations.
Now, his investigation is contributing to the ongoing first-in-human early feasibility trial of closed-loop neuromodulation of the nucleus accumbens for Loss of Control Eating. He is also working on the design of innovative, invasive clinical studies for conditions like Obsessive Compulsive Disorder. He is committed to investigate cutting-edge neuroimaging and neurophysiology modalities, including diffusion magnetic resonance imaging, as well as novel brain-clearing techniques to improve stereotactic targeting neuromodulation for pathological impulsivity, a pervasive symptom in a wide range of neurological and neuropsychiatric disorders.
M.D., Universidade Federal do Estado do Rio de Janeiro (2018)
Accumbens coordinated reset stimulation in mice exhibits ameliorating aftereffects on binge alcohol drinking.
Alcohol use disorder (AUD) affects nearly 5% of the world's adult population. Despite treatment, AUD often manifests with relapse to binge drinking, which has been associated with corticostriatal hypersynchrony involving the nucleus accumbens (NAc).A modified "Drinking in the Dark" protocol was used to provoke binge-like alcohol drinking. We implemented Coordinated Reset Stimulation (CRS), a computationally designed, spatio-temporal stimulation algorithm, to desynchronize abnormal neuronal activity via a deep brain stimulation (DBS) electrode in the NAc of mice exhibiting binge-like alcohol drinking. Integral CRS charge injected would be 2.5% of that of conventional high-frequency DBS.NAc CRS delivery during only the initial phase of exposure to alcohol and prior to the exposure (but not during) significantly reduced binge-like drinking without interfering with social behavior or locomotor activity.NAc CRS ameliorates binge-like alcohol drinking and preliminarily exhibits sustained aftereffects that are suggestive of an unlearning of hypersynchrony.
View details for DOI 10.1016/j.brs.2021.01.015
View details for PubMedID 33524612
Brain-Responsive Neurostimulation for Loss of Control Eating: Early Feasibility Study.
Loss of control (LOC) is a pervasive feature of binge eating, which contributes significantly to the growing epidemic of obesity; approximately 80 million US adults are obese. Brain-responsive neurostimulation guided by the delta band was previously found to block binge-eating behavior in mice. Following novel preclinical work and a human case study demonstrating an association between the delta band and reward anticipation, the US Food and Drug Administration approved an Investigational Device Exemption for a first-in-human study.To assess feasibility, safety, and nonfutility of brain-responsive neurostimulation for LOC eating in treatment-refractory obesity.This is a single-site, early feasibility study with a randomized, single-blinded, staggered-onset design. Six subjects will undergo bilateral brain-responsive neurostimulation of the nucleus accumbens for LOC eating using the RNS® System (NeuroPace Inc). Eligible participants must have treatment-refractory obesity with body mass index ≥ 45 kg/m2. Electrophysiological signals of LOC will be characterized using real-time recording capabilities coupled with synchronized video monitoring. Effects on other eating disorder pathology, mood, neuropsychological profile, metabolic syndrome, and nutrition will also be assessed.Safety/feasibility of brain-responsive neurostimulation of the nucleus accumbens will be examined. The primary success criterion is a decrease of ≥1 LOC eating episode/week based on a 28-d average in ≥50% of subjects after 6 mo of responsive neurostimulation.This study is the first to use brain-responsive neurostimulation for obesity; this approach represents a paradigm shift for intractable mental health disorders.
View details for DOI 10.1093/neuros/nyaa300
View details for PubMedID 32717033
An Open-Label Clinical Trial of Hypothalamic Deep Brain Stimulation for Human Morbid Obesity: BLESS Study Protocol.
Human morbid obesity is increasing worldwide in an alarming way. The hypothalamus is known to mediate its mechanisms. Deep brain stimulation (DBS) of the ventromedial hypothalamus (VMH) may be an alternative to treat patients refractory to standard medical and surgical therapies.To assess the safety, identify possible side effects, and to optimize stimulation parameters of continuous VMH-DBS. Additionally, this study aims to determine if continuous VMH-DBS will lead to weight loss by causing changes in body composition, basal metabolism, or food intake control.The BLESS study is a feasibility study, single-center open-label trial. Six patients (body mass index > 40) will undergo low-frequency VMH-DBS. Data concerning timing, duration, frequency, severity, causal relationships, and associated electrical stimulation patterns regarding side effects or weight changes will be recorded.We expect to demonstrate the safety, identify possible side effects, and to optimize electrophysiological parameters related to VMH-DBS. No clinical or behavioral adverse changes are expected. Weight loss ≥ 3% of the basal weight after 3 mo of electrical stimulation will be considered adequate. Changes in body composition and increase in basal metabolism are expected. The amount of food intake is likely to remain unchanged.The design of this study protocol is to define the safety of the procedure, the surgical parameters important for target localization, and additionally the safety of long-term stimulation of the VMH in morbidly obese patients. Novel neurosurgical approaches to treat metabolic and autonomic diseases can be developed based on the data made available by this investigation.
View details for DOI 10.1093/neuros/nyy024
View details for PubMedID 29538761
The hypothalamus at the crossroads of psychopathology and neurosurgery
2017; 43 (3): E15
The neurosurgical endeavor to treat psychiatric patients may have been part of human history since its beginning. The modern era of psychosurgery can be traced to the heroic attempts of Gottlieb Burckhardt and Egas Moniz to alleviate mental symptoms through the ablation of restricted areas of the frontal lobes in patients with disabling psychiatric illnesses. Thanks to the adaptation of the stereotactic frame to human patients, the ablation of large volumes of brain tissue has been practically abandoned in favor of controlled interventions with discrete targets. Consonant with the role of the hypothalamus in the mediation of the most fundamental approach-avoidance behaviors, some hypothalamic nuclei and regions, in particular, have been selected as targets for the treatment of aggressiveness (posterior hypothalamus), pathological obesity (lateral or ventromedial nuclei), sexual deviations (ventromedial nucleus), and drug dependence (ventromedial nucleus). Some recent improvements in outcomes may have been due to the use of stereotactically guided deep brain stimulation and the change of therapeutic focus from categorical diagnoses (such as schizophrenia) to dimensional symptoms (such as aggressiveness), which are nonspecific in terms of formal diagnosis. However, agreement has never been reached on 2 related issues: 1) the choice of target, based on individual diagnoses; and 2) reliable prediction of outcomes related to individual targets. Despite the lingering controversies on such critical aspects, the experience of the past decades should pave the way for advances in the field. The current failure of pharmacological treatments in a considerable proportion of patients with chronic disabling mental disorders is reminiscent of the state of affairs that prevailed in the years before the early psychosurgical attempts. This article reviews the functional organization of the hypothalamus, the effects of ablation and stimulation of discrete hypothalamic regions, and the stereotactic targets that have most often been used in the treatment of psychopathological and behavioral symptoms; finally, the implications of current and past experience are presented from the perspective of how this fund of knowledge may usefully contribute to the future of hypothalamic psychosurgery.
View details for DOI 10.3171/2017.6.FOCUS17256
View details for Web of Science ID 000410299800009
View details for PubMedID 28859567
Anticipatory human subthalamic area beta-band power responses to dissociable tastes correlate with weight gain.
Neurobiology of disease
The availability of enticing sweet, fatty tastes is prevalent in the modern diet and contribute to overeating and obesity. In animal models, the subthalamic area plays a role in mediating appetitive and consummatory feeding behaviors, however, its role in human feeding is unknown. We used intraoperative, subthalamic field potential recordings while participants (n = 5) engaged in a task designed to provoke responses of taste anticipation and receipt. Decreased subthalamic beta-band (15-30 Hz) power responses were observed for both sweet-fat and neutral tastes. Anticipatory responses to taste-neutral cues started with an immediate decrease in beta-band power from baseline followed by an early beta-band rebound above baseline. On the contrary, anticipatory responses to sweet-fat were characterized by a greater and sustained decrease in beta-band power. These activity patterns were topographically specific to the subthalamic nucleus and substantia nigra. Further, a neural network trained on this beta-band power signal accurately predicted (AUC ≥ 74%) single trials corresponding to either taste. Finally, the magnitude of the beta-band rebound for a neutral taste was associated with increased body mass index after starting deep brain stimulation therapy. We provide preliminary evidence of discriminatory taste encoding within the subthalamic area associated with control mechanisms that mediate appetitive and consummatory behaviors.
View details for DOI 10.1016/j.nbd.2021.105348
View details for PubMedID 33781923
Anatomical feasibility of peripheral nerve transfer to reestablish external anal sphincter control - cadaveric study.
Surgical and radiologic anatomy : SRA
PURPOSE: Motor deficits affecting anal sphincter control can severely impair quality of life. Peripheral nerve transfer has been proposed as an option to reestablish anal sphincter motor function. We assessed, in human cadavers, the anatomical feasibility of nerve transfer from a motor branch of the tibialis portion of the sciatic nerve to two distinct points on pudendal nerve (PN), through transgluteal access, as a potential approach to reestablish anal sphincter function.METHODS: We dissected 24 formalinized specimens of the gluteal region and posterior proximal third of the thigh. We characterized the motor fascicle (donor nerve) from the sciatic nerve to the long head of the biceps femoris muscle and the PN (recipient nerve), and measured nerve lengths required for direct coaptation from the donor nerve to the recipient in both the gluteal region (proximal) and perineal cavity (distal).RESULTS: We identified three anatomical variations of the donor nerve as well as three distinct branching patterns of the recipient nerve from the piriformis muscle to the pudendal canal region. Donor nerve lengths (proximal and distal) were satisfactory for direct coaptation in all cases.CONCLUSIONS: Transfer of a motor fascicle of the sciatic nerve to the PN is anatomically feasible without nerve grafts. Donor nerve length was sufficient and donor nerve functionally compatible (motor). Anatomical variations in the PN could also be accommodated.
View details for DOI 10.1007/s00276-020-02635-z
View details for PubMedID 33386457
Brain-wide unbiased mapping of neuronal activity pinpoints ketamine's interaction with the opioid system in mice
LIPPINCOTT WILLIAMS & WILKINS. 2020: 415
View details for Web of Science ID 000619264500195
Electrophysiology and Structural Connectivity of the Posterior Hypothalamic Region: Much to Learn From a Rare Indication of Deep Brain Stimulation.
Frontiers in human neuroscience
2020; 14: 164
Cluster headache (CH) is among the most common and debilitating autonomic cephalalgias. We characterize clinical outcomes of deep brain stimulation (DBS) to the posterior hypothalamic region through a novel analysis of the electrophysiological topography and tractography-based structural connectivity. The left posterior hypothalamus was targeted ipsilateral to the refractory CH symptoms. Intraoperatively, field potentials were captured in 1 mm depth increments. Whole-brain probabilistic tractography was conducted to assess the structural connectivity of the estimated volume of activated tissue (VAT) associated with therapeutic response. Stimulation of the posterior hypothalamic region led to the resolution of CH symptoms, and this benefit has persisted for 1.5-years post-surgically. Active contacts were within the posterior hypothalamus and dorsoposterior border of the ventral anterior thalamus (VAp). Delta- (3 Hz) and alpha-band (8 Hz) powers increased and peaked with proximity to the posterior hypothalamus. In the posterior hypothalamus, the delta-band phase was coupled to beta-band amplitude, the latter of which has been shown to increase during CH attacks. Finally, we identified that the VAT encompassing these regions had a high proportion of streamlines of pain processing regions, including the insula, anterior cingulate gyrus, inferior parietal lobe, precentral gyrus, and the brainstem. Our unique case study of posterior hypothalamic region DBS supports durable efficacy and provides a platform using electrophysiological topography and structural connectivity, to improve mechanistic understanding of CH and this promising therapy.
View details for DOI 10.3389/fnhum.2020.00164
View details for PubMedID 32670034
View details for PubMedCentralID PMC7326144
Upholding Scientific Duty Amidst Poisonous Disinformation.
2020; 12 (7): e9339
Because of a recent politically-biased Lancet editorial, the world's opinion has been directed against the Brazilian government over the rising numbers of COVID-19 cases in the country. This is an example of reporting data without accounting for important covariates. Epidemiological figures should always be corrected for population size. In fact, Brazil is not even on the list of the 10 countries with the highest number of deaths per 100,000 people. Belgium, the United Kingdom, and Spain are the most affected countries in this regard. The disinformation presented by a renowned medical journal has ignited severe criticisms against a Chief-of-State for not promoting a generalized lockdown in a country of continental size. As scientists, we have a duty to stress the caveats of science instead of fueling political attacks, and we should refrain from jumping to uninformed conclusions without considering well-analyzed data. Moreover, while there is no evidence to endorse the efficacy of a generalized lockdown in socioeconomically vulnerable populations, it is undoubtedly associated with severe nationwide adverse effects.
View details for DOI 10.7759/cureus.9339
View details for PubMedID 32850213
View details for PubMedCentralID PMC7444859
Evidence for the role of the dorsal ventral lateral posterior thalamic nucleus connectivity in deep brain stimulation for Gilles de la Tourette syndrome.
Journal of psychiatric research
2020; 132: 60–64
Gilles de la Tourette syndrome (GTS) can manifest as debilitating, medically-refractory tics for which deep brain stimulation (DBS) of the centromedian-parafascicular complex (CM) can provide effective treatment. However, patients have reported benefit with activation of contacts dorsal to the CM and likely in the ventro-lateral thalamus (VL). At our institution, a case of a robust and durable response in a GTS patient required stimulation in the CM and more dorsally. We explore the structural connectivity of thalamic subregions associated with GTS using diffusion MRI tractography. Diffusion weighted images from 40 healthy Human Connectome Project (HCP) subjects and our GTS patient were analyzed. The VL posterior nucleus (VLp) and the CM were used as seeds for whole-brain probabilistic tractography. Leads were localized via linear registration of pre-/post-operative imaging and cross-referenced with the DBS Intrinsic Template Atlas. Tractography revealed high streamline probability from the CM and VLp to the superior frontal gyrus, rostral middle frontal gyrus, brainstem, and ventral diencephalon. Given reported variable responses to DBS along the thalamus, we segmented the VLp based on its connectivity profile. Ventral and dorsal subdivisions emerged, with streamline probability patterns differing between the dorsal VLp and CM. The CM, the most reported DBS target for GTS, and the dorsal VLp have different but seemingly complimentary connectivity profiles as evidenced by our patient who, at 1-year post-operatively, had significant therapeutic benefit. Stimulation of both regions may better target reward and motor circuits, resulting in enhanced symptom control for GTS.
View details for DOI 10.1016/j.jpsychires.2020.09.024
View details for PubMedID 33045620
Multiparametric laryngeal assessment of the effect of thalamic deep brain stimulation on essential vocal tremor.
Parkinsonism & related disorders
2020; 81: 106–12
EVT is a refractory voice disorder that significantly affects quality of life. This work aims to conduct a multiparametric assessment of the effect of deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) on essential vocal tremor (EVT) and investigate the relation between DBS lead location and EVT outcomes.Nine participants underwent DBS for essential tremor and were diagnosed with co-occurring EVT in this prospective cohort study. Objective measurements including acoustic evaluation of vocal fundamental frequency (F0) and intensity modulation and subjective measurements including physiologic evaluation of the oscillatory movement of the laryngeal muscles and vocal tract and perceptual ratings of tremor severity were collected PRE and POST DBS. Finally, we investigated the relation between DBS lead location and EVT outcomes.Acoustic modulations of F0 and intensity were significantly improved POST DBS. Physiologic assessment showed a POST DBS reduction of oscillatory movement in the laryngeal muscles and vocal tract, but not significantly. Listener and participant perception, of EVT severity was also significantly reduced. Finally, our results indicate better EVT control with increased distance to midline of left VIM thalamic stimulation.By employing a battery of objective and subjective measures, our study supports the benefit of DBS for the treatment of EVT and specifies the acoustic and physiologic mechanisms that mediate its positive effect. We further provide preliminary results on the relation between lead location and EVT outcomes, laying the foundation for future studies to clarify the optimal DBS target for the treatment of EVT.
View details for DOI 10.1016/j.parkreldis.2020.10.026
View details for PubMedID 33120071
Case Report on Deep Brain Stimulation Rescue After Suboptimal MR-Guided Focused Ultrasound Thalamotomy for Essential Tremor: A Tractography-Based Investigation.
Frontiers in human neuroscience
2020; 14: 191
Essential tremor (ET) is the most prevalent movement disorder in adults, and can often be medically refractory, requiring surgical intervention. MRI-guided focused ultrasound (MRgFUS) is a less invasive procedure that uses ultrasonic waves to induce lesions in the ventralis intermedius nucleus (VIM) to treat refractory ET. As with all procedures for treating ET, optimal targeting during MRgFUS is essential for efficacy and durability. Various studies have reported cases of tremor recurrence following MRgFUS and long-term outcome data is limited to 3-4 years. We present a tractography-based investigation on a case of DBS rescue for medically refractory ET that was treated with MRgFUS that was interrupted due to the development of dysarthria during the procedure. After initial improvement, her hand tremor started to recur within 6 months after treatment, and bilateral DBS was performed targeting the VIM 24 months after MRgFUS. DBS induced long-term tremor control with monopolar stimulation. Diffusion MRI tractography was used to reconstruct the dentatorubrothalamic (DRTT) and corticothalmic (CTT) tracts being modulated by the procedures to understand the variability in efficacy between MRgFUS and DBS in treating ET in our patient. By comparing the MRgFUS lesion and DBS volume of activated tissue (VAT), we found that the MRgFUS lesion was located ventromedially to the VAT, and was less than 10% of the size of the VAT. While the lesion encompassed the same proportion of DRTT streamlines, it encompassed fewer CTT streamlines than the VAT. Our findings indicate the need for further investigation of targeting the CTT when using neuromodulatory procedures to treat refractory ET for more permanent tremor relief.
View details for DOI 10.3389/fnhum.2020.00191
View details for PubMedID 32676015
View details for PubMedCentralID PMC7333679
Pediatric peripheral nerve tumors: clinical and surgical aspects.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
Pediatric peripheral nerve tumors (PNTs) are rare. Most are related to neurofibromatosis type 1 (NF1) with the potential for malignancy. An ongoing debate occurs about the best approach to such patients. This study describes a cohort of pediatric patients with PNTs and discusses clinical characteristics and surgical treatment.We retrospectively reviewed the charts of seven pediatric patients with eight PNTs surgically treated from 2007 to 2018. Information concerning patient demographics, clinical presentation, PNTs characteristics, treatment choice, and outcome were recorded.All children presented with intense pain and a palpable mass. Three of the eight tumors were associated with a neurological deficit. Among the four patients with NF1, two had a neurofibroma and two a malignant peripheral nerve sheath tumor (MPNST). Histologically, three of the lesions were a benign peripheral nerve sheath tumor (BPNST), three a MPNST, and one each a desmoid tumor and Ewing's sarcoma. Two of the eight tumors underwent partial tumor excision and six gross total excisions.Intense pain at rest, day, and/or night, preventing normal activities; a palpable, hard, immobile mass; an intense Tinel's sign related to the lump; clinical evidence of NF1; and high-speed growth of a tumor in the trajectory of the nerve or plexus should alert the clinician to the potential for malignancy. Preoperative biopsy is not indicated when clinical and imaging findings suggest a benign tumor. The surgical management of PNTs must be to achieve total resection, including wide margins with malignant tumors, though this is not always possible.
View details for DOI 10.1007/s00381-019-04306-w
View details for PubMedID 31346736
A Neglected Cause of Iatrogenic Brachial Plexus Injuries in Psychiatric Patients
2018; 82 (3): 307–11
Psychiatric patients are often kept immobilized during hospitalization to avoid self-inflicted injuries and danger to third parties. Inadequate positioning can lead to brachial plexus injuries (BPI).To present a series of 5 psychiatric patients with BPI after being left sedated and restrained for prolonged periods of time during hospitalization.We retrospectively reviewed the charts of 5 psychiatric patients with iatrogenic BPI referred by other institutions to our service. The restraint technique adopted by those institutions consisted of a high-thoracic restraint. All patients underwent complete clinical and neurological examination at our center. Information concerning patient demographics, BPI characteristics, treatment choice, and ultimate outcome was recorded.Three patients were male. The age of our patients ranged from 25 to 61 years old (mean: 41.2; median: 43). Three patients had a diagnosis of bipolar disorder while 2 had schizophrenia. Duration of immobilization ranged from 5 to 168 h (mean: 77.8; median: 72). Four patients presented with a unilateral right-sided lesion. Time to presentation ranged from 1 to 9 mo (mean: 4.2; median: 4). All patients also had intense pain and axillary lesions. Four patients received conservative treatment with partial or full functional recovery and complete pain resolution. The remaining patients underwent surgical repair and experienced good functional outcome.Psychiatric patients who need to be sedated and immobilized must be monitored closely, as BPI can occur from high-thoracic restraints. When such an injury occurs, the patient must be referred to a center specialized in peripheral nerve surgery and rehabilitation.
View details for DOI 10.1093/neuros/nyx162
View details for Web of Science ID 000439685800023
View details for PubMedID 28521032
Double Blinded Randomized Trial of Subcutaneous Trigeminal Nerve Stimulation as Adjuvant Treatment for Major Unipolar Depressive Disorder.
More than 30% of major depressive disorder patients fail to respond to adequate trials of medications and psychotherapy. While modern neuromodulation approaches (ie, vagal nerve stimulation, deep brain stimulation) are yet to prove their efficacy for such cases in large randomized controlled trials, trigeminal nerve stimulation (TNS) has emerged as an alternative with promising effects on mood disorders.To assess efficacy, safety, tolerability, and placebo effect duration of continuous subcutaneous TNS (sTNS) in treatment-resistant depression (TRD).The TREND study is a single-center, double-blind, randomized, controlled, phase II clinical trial. Twenty unipolar TRD patients will receive V1 sTNS as adjuvant to medical therapy and randomized to active vs sham stimulation throughout a 24-wk period. An additional 24-wk open-label phase will follow. Data concerning efficacy, placebo response, relapse, and side effects related to surgery or electrical stimulation will be recorded. We will use the HDRS-17, BDI-SR, IDS_SR30, and UKU scales.The main outcome measure is improvement in depression scores using HAM-17 under continuous sTNS as adjuvant to antidepressants. Active stimulation is expected to significantly impact response and remission rates. Minor side effects are expected due to the surgical procedure and electrical stimulation. The open-label phase should further confirm efficacy and tolerability.This study protocol is designed to define efficacy of a novel adjuvant therapy for TRD. We must strive to develop safe, reproducible, predictable, and well-tolerated neuromodulation approaches for TRD patients impaired to manage their lives and contribute with society.
View details for DOI 10.1093/neuros/nyy420
View details for PubMedID 30272245